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Full-term Pregnancy Induces a Specific Genomic Signature in the Human Breast

Breast cancer risk has traditionally been linked to nulliparity or late first full-term pregnancy, whereas young age at first childbirth, multiparity, and breast-feeding are associated with a reduced risk. Early pregnancy confers protection by inducing breast differentiation, which imprints a specif...

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Published in:Cancer epidemiology, biomarkers & prevention biomarkers & prevention, 2008-01, Vol.17 (1), p.51-66
Main Authors: RUSSO, Jose, BALOGH, Gabriela A, RUSSO, Irma H
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description Breast cancer risk has traditionally been linked to nulliparity or late first full-term pregnancy, whereas young age at first childbirth, multiparity, and breast-feeding are associated with a reduced risk. Early pregnancy confers protection by inducing breast differentiation, which imprints a specific and permanent genomic signature in experimental rodent models. For testing whether the same phenomenon was detectable in the atrophic breast of postmenopausal parous women, we designed a case-control study for the analysis of the gene expression profile of RNA extracted from epithelial cells microdissected from normal breast tissues obtained from 18 parous and 7 nulliparous women free of breast pathology (controls), and 41 parous and 8 nulliparous women with history of breast cancer (cases). RNA was hybridized to cDNA glass microarrays containing 40,000 genes; arrays were scanned and the images were analyzed using ImaGene software version 4.2. Normalization and statistical analysis were carried out using Linear Models for Microarrays and GeneSight software for hierarchical clustering. The parous control group contained 2,541 gene sequences representing 18 biological processes that were differentially expressed in comparison with the other three groups. Hierarchical clustering of these genes revealed that the combined parity/absence of breast cancer data generated a distinct genomic profile that differed from those of the breast cancer groups, irrespective of parity history, and from the nulliparous cancer-free group, which has been traditionally identified as a high-risk group. The signature that identifies those women in whom parity has been protective will serve as a molecular biomarker of differentiation for evaluating the potential use of preventive agents. (Cancer Epidemiol Biomarkers Prev 2008;17(1):51–66)
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Early pregnancy confers protection by inducing breast differentiation, which imprints a specific and permanent genomic signature in experimental rodent models. For testing whether the same phenomenon was detectable in the atrophic breast of postmenopausal parous women, we designed a case-control study for the analysis of the gene expression profile of RNA extracted from epithelial cells microdissected from normal breast tissues obtained from 18 parous and 7 nulliparous women free of breast pathology (controls), and 41 parous and 8 nulliparous women with history of breast cancer (cases). RNA was hybridized to cDNA glass microarrays containing 40,000 genes; arrays were scanned and the images were analyzed using ImaGene software version 4.2. Normalization and statistical analysis were carried out using Linear Models for Microarrays and GeneSight software for hierarchical clustering. 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ispartof Cancer epidemiology, biomarkers & prevention, 2008-01, Vol.17 (1), p.51-66
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subjects Aged
Aged, 80 and over
Biological and medical sciences
Biomarkers, Tumor - genetics
Biomarkers, Tumor - metabolism
breast cancer risk
breast differentiation
Breast Neoplasms - genetics
Breast Neoplasms - metabolism
Breast Neoplasms - pathology
Carcinoma, Ductal, Breast - genetics
Carcinoma, Ductal, Breast - metabolism
Carcinoma, Ductal, Breast - pathology
Case-Control Studies
Female
Gene Expression Profiling
Gene Expression Regulation, Neoplastic - physiology
genomic signature
Humans
Medical sciences
Middle Aged
Neoplasm Invasiveness - pathology
nulliparity
Oligonucleotide Array Sequence Analysis
Pregnancy
Reverse Transcriptase Polymerase Chain Reaction
Tumors
title Full-term Pregnancy Induces a Specific Genomic Signature in the Human Breast
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